title: The pro-form of BMP-2 exhibits a delayed and reduced activity when compared to mature BMP-2.
abstract: Pro-forms of growth factors receive increasing attention since it was shown that they can affect the function(s) of the mature proteins. Here, we extend our previous investigations on the biological function of the pro-form of bone morphogenetic protein-2 (BMP-2). We demonstrate that proBMP-2, upon prolonged incubation with C2C12 cells, induces alkaline phosphatase, a marker enzyme for osteoblastic differentiation. Expression studies with three different bone marker transcripts reveal that proBMP-2 induces bone-specific transcripts, however, to a smaller extent than the mature growth factor. To resolve this finding at the protein level, the fate of proBMP-2 and BMP-2 was studied in cell culture. We demonstrate that both proteins become internalized, and proBMP-2 is processed to mature BMP-2 within the cells. The data presented here suggest that proBMP-2 elicits biological functions as mature BMP-2 at a delayed and reduced level, which might depend on intracellular cleavage and subsequent secretion as mature BMP-2.
authors.affiliation: Institut für Biochemie und Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany. sabrina.voneinem@biochemtech.uni-halle.de
authors.forename: Sabrina
authors.initials: S
authors.lastname: von Einem
authors.forename: Silvio
authors.initials: S
authors.lastname: Erler
authors.forename: Katrin
authors.initials: K
authors.lastname: Bigl
authors.forename: Bernhard
authors.initials: B
authors.lastname: Frerich
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schwarz
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2; D011498:Protein Precursors; D014157:Transcription Factors; D015675:Osteocalcin; D000469:Alkaline Phosphatase